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Postoperative adjuvant therapy has been indicated by advanced T classification for T3–4 oral squamous cell carcinoma (OSCC) and the significance of perineural invasion (PNI) and lymphovascular invasion (LVI) in treatment for T3–4 OSCC remains unclear. Ninety-eight cumulative patients with T3–4 OSCC who underwent curative surgery between Jan 2002 and Dec 2010 were recruited and analyzed. Twenty-seven (27.6%) patients were PNI/LVI double positive. PNI/LVI double positive demonstrated independent predictive values for higher neck metastasis (LN+), higher distant metastasis (DM) and low 5-year disease-specific survival (DSS) rates (p p = 0.017, and p

Background To assess the feasibility of tongue conservation treatment with induction chemotherapy (ICT), tongue conservation surgery, and risk‐adapted postoperative adjuvant therapy in oral tongue squamous cell carcinoma (OTSCC). Methods Patients with newly diagnosed OTSCC cT2‐4 N0‐2 M0 were recruited. The ICT with a regimen of docetaxel, cisplatin, and oral tegafur/uracil (DCU) was administrated every 21 days. After the first cycle of ICT (DCU1), patients with a more than 30% decrease in the longest diameter of primary tumor underwent a second cycle of ICT (DCU2). Tongue conservation surgery was performed after ICT, and risk‐adapted adjuvant therapy was organized based on pathological features. Results From July 2011 to December 2015, a total of 23 patients were enrolled, 87% of whom were classified as stage III–IV. Clinical responders to DCU1 and DCU2 were determined in 90.5% (19/21) and 88.2% (15/17) of patients. Tongue conservation surgery was performed in 16 responders to ICT. Only one patient had a positive margin (6.3%), and a complete pathologic response was achieved in eight patients (50%). Only one patient developed local recurrence after a median follow‐up of 58.6 months (range, 7.9–105.2). The 5‐year overall survival (0% vs. 87.5%, P = 0.001) and disease‐specific survival (0% vs. 93.3%, P = 0.000) were significantly different between the DCU1 nonresponders and responders. Conclusion Tongue conservation treatment with ICT, followed by conservation surgery and risk‐adapted adjuvant therapy, is feasible for patients with OTSCC who are good responders to ICT. However, the outcomes of nonresponders are dismal. Further study in a larger patient population is warranted.

Objective: To determine the role of upfront neck dissection (ND) in patient survival and regional control of p16-negative oropharyngeal squamous cell carcinoma (OPSCC) with neck metastases. Design: Retrospective study. Participants: Patients with p16-negative OPSCC with neck metastases, diagnosed between January 1, 2011 and December 31, 2017, and treated with upfront ND followed by chemoradiotherapy (ND + CCRT) or primary chemoradiotherapy (CCRT). Main outcome measures: Recurrence and survival rates were analysed using the Kaplan-Meier method. Results: Data of 67 patients with p16-negative cN+ OPSCC were analysed. Of them, 23 (34.3%) received ND + CCRT and 44 (65.7%) received primary CCRT. At a median follow-up of 37.9 months, the 3-year neck recurrence rate was significantly lower in the ND + CCRT group than in the CCRT group (0% vs. 19%, p=0.031). This trend was more obvious in patients with neck metastases ≥3 cm (0% vs. 32.1%, p=0.045). Survival outcomes were comparable between the groups; notably, the ND + CCRT group received a significantly lower dose of radiotherapy (3-year disease-specific survival: 77.3% and 75.3%, p=0.968, respectively; 3-year disease-free survival: 77.3% and 70.1%, p=0.457, respectively; 3-year overall survival: 62% and 61.8%, p=0.771, respectively between the ND + CCRT and CCRT groups). Conclusion: Upfront ND was significantly beneficial for regional control and resulted in comparable oncological outcomes with a significantly reduced radiation dose. These results findings can help guide the development of a standardised treatment plan for p16-negative OPSCC. Additional prospective studies with larger sample sizes are warranted.

BackgroundAngiopoietin-Tie2 and nitric oxide pathway is crucial in tumor angiogenesis and closely correlates with tumor development, growth, and metastasis. This study aimed to investigate the angiopoietin-Tie2 and nitric oxide signaling of the erythrocyte membrane in response to surgical trauma in head and neck cancer.MethodsWe prospectively enrolled the patients with histology-proven head and neck squamous cell carcinoma undergoing surgical resection of primary tumors at the medical center between August and November 2019. We measured the preoperative and postoperative levels of angiopoietin-1, angiopoietin-2 in plasma using enzyme-linked immunosorbent assays, nitric oxide in plasma using nitrate/nitrite colorimetric assays, and Tie2 phosphorylation in erythrocyte membrane using Western blotting.ResultsThe plasma angiopoietin-1 was downregulated from the median 971.3 pg/mL (interquartile range [IQR] 532.1–1569.3) to 417.9 (IQR 270.5–597.3) after tumor resection (p= 0.0020). Conversely, the plasma angiopoietin-2 was enhanced from 1173.6 pg/mL (IQR 977.7–1450.2) to 2353.7 (IQR 1352.4–2954.3) after surgery (p= 0.0021), with a concomitant increase in plasma nitric oxide level from 7.73 μM (IQR 5.39–10.06) to 10.50 (IQR 7.65–14.18) after surgical resection (p= 0.0093). Subgroup analyses further showed the angiopoietin-Tie2 and nitric oxide signaling was significant only in stage III and IV cancer.ConclusionsThe dynamic change of angiopoietin-Tie2 signaling in the erythrocyte membrane along with the enhanced nitric oxide in plasma after tumor resection suggests erythrocytes play a significant role in modulating surgery-induced angiogenesis, which may provide a novel marker for cancer surveillance and control.

Perineural invasion (PNI) has been an established poor prognostic feature for T1-T2 oral squamous cell carcinoma (OSCC). Different presentations and amounts of PNI are commonly observed, but PNI is currently recorded as being present or absent. This study asked whether the quantification of PNI provides additional information for early OSCC.Retrospective cohort study.Tertiary referral medical center.Pathologic reevaluations were performed for 314 patients with T1-T2 OSCC who underwent curative surgery from June 2001 to August 2009. A novel parameter, PNI focus number, was defined for PNI quantification. With 5 PNI foci as the cutoff, patients were categorized into 3 groups: no PNI (0 PNI foci), low PNI (PNI foci, 1-5), and high PNI (PNI foci5). Rate of cervical lymph node metastasis (LN+), 5-year disease-specific survival (DSS), and 5-year overall survival (OS) were analyzed among these groups.PNI focus number independently predicted for LN+, poor DSS, and poor OS in multivariate analysis after controlling for T classification, lymphovascular invasion, differentiation, margin, and tumor thickness. The 5-year DSS demonstrated a dose-dependent decrease among the 3 groups (no PNI, 88.6%; low PNI, 75.2%; high PNI, 33.8%; P.001). Moreover, the 5-year DSS of the high PNI group was significantly worse than that of the low PNI group.PNI focus number can be a novel parameter for PNI quantification in early OSCC. Although optimal quantification methods still require further investigation, this study offers clear clinical support for the nerve-tumor interaction hypothesis and advocates further mechanistic research for the exploration of PNI-related treatment concepts for OSCC.

Background To evaluate the failure pattern and identify predictors of locoregional control in lateralized buccogingival cancer after postoperative radiotherapy (RT) at a single institution. Methods We retrospectively reviewed the clinical data of 150 patients with lateralized oral squamous cell carcinoma, including carcinoma of the buccal mucosa, gingiva and retromolar trigone. All patients underwent radical surgery followed by postoperative RT with or without concurrent chemotherapy. We registered planning computer tomography images with images obtained at recurrence and categorized the failure pattern as in-field, marginal, or out-field recurrence. Results The median follow-up duration was 47 months (range, 2–131 months). Twenty-eight patients (19%) experienced locoregional failure, including 20 local failure, 5 regional failure and 3 with both. Among the 24 patients who had image studies at recurrence, 15 patients had in-field recurrence, 5 were marginal recurrence and 4 were out-field recurrence. Seven patients (5%) had contralateral neck failure. Four of 5 patients with marginal failure had recurrent tumors in the infratemporal fossa. In multivariate analysis, extracapsular spread and positive or close surgical margin were associated with poor locoregional control. Conclusion Local in-field recurrence is the most common failure pattern in lateralized buccogingival cancer after postoperative RT. The infratemporal fossa is a risk area for marginal failure and should be encompassed adequately in the postoperative RT field. Extracapsular spread and positive or close margin are predictors of locoregional control for lateralized oral cancer. Patients exhibiting such adverse features require more aggressive treatment.

Background Inoperable oral cavity squamous cell carcinoma (SCC) is a highly invasive disease associated with the extensive destruction of locoregional tissues and a dismal prognosis. Management strategies for these patients are limited. Methods This study was a single arm, prospective, open-label phase II trial. A regimen consisting of cetuximab-docetaxel, cisplatin, and fluorouracil (C-TPF) followed by bio-chemoradiotherapy (bio-CRT) with cisplatin and cetuximab was administered to patients who responded to induction chemotherapy. The objective response rate to C-TPF was the primary endpoint. Results Forty-three patients were enrolled in this study. The objective response rate of C-TPF was 88.4%; 88.9% (32/36) of the responders completed the full bio-CRT course, and the objective response rate of bio-CRT was 64.7%. The most common grade 3/4 adverse events for induction chemotherapy were leucopenia (32.6%) and febrile neutropenia (14.0%). The 1-year progression-free survival (PFS) and overall survival (OS) rates were 43% and 68%, respectively. Conclusion C-TPF is an effective and tolerable induction chemotherapy regimen for inoperable oral cavity SCC.

Early enzyme replacement therapy (ERT) improve long-term outcomes in patients with infantile-onset Pompe disease (IOPD). Our cohort of patients with IOPD at Taipei Veterans General Hospital (TVGH) joined Taiwan Pompe newborn screening program from 2008, testing more than one million newborns until 2018. By 2010, we had established rapid diagnostic strategies. Now, the average age of ERT initiation starts at an average age of

Objective This paper aims to comprehensively document a rare case of thyroid carcinoma with rhabdoid phenotype and literature review of this disease. Methods A 59-year-old man presented with a rapidly enlarging, painful left lateral cervical mass. CT scan revealed a tumor over the left the thyroid gland with multiple left cervical lymphadenopathy over left level II–IV and level VI. Fine-needle aspiration cytology reported carcinoma, type undetermined. Total thyroidectomy with central compartment and left neck dissection was performed. Results Pathology report showed rhabdoid phenotype of thyroid carcinoma. Final staging was pT4N1M1. Conclusions Although WHO classification of thyroid tumor histology does not define this disease entity, few cases were reported. In the last 20 years, English literature review revealed only 12 cases about thyroid carcinoma with rhabdoid phenotype. Major treatment of thyroid carcinoma with rhabdoid phenotype is surgery, and the benefit of adjuvant therapies as radiotherapy or systemic chemotherapy is not clear. The prognosis of thyroid carcinoma with rhabdoid phenotype is extremely poor, with mean survival of only 6 months.

Objectives Perineural invasion (PNI) is a poor prognostic pathologic feature of oral squamous cell carcinoma (OSCC). The mechanisms of PNI remain poorly understood, and nerve-tumour interactions have been implicated for its pathogenesis. Design and setting Systematic investigation of nerve-tumour interactions was performed using fresh human peripheral nerve. In vitro and in vivo models were used to determine the ability of human peripheral nerves to enhance OSCC migration/invasion. Retrospective cohort study was also carried out in one medical centre from 2001 to 2009. Participants 314 T1-2 OSCC patients. Main outcome measures In the transwell migration/invasion assay, the cells in five representative fields were counted. In the nerve implantation model, tumour size was estimated. PNI quantification by PNI focus number was carried out in the OSCC patients to correlate with cervical lymph node metastasis and oncologic outcomes. Results The transwell migration/invasion assay demonstrated that human peripheral nerves, compared with subcutaneous soft tissue, significantly enhanced the migration/invasion abilities of OSCC. Moreover, the enhanced migration was dose-dependent with increased length or number of peripheral nerve segments. The nerve implantation model showed that human peripheral nerve also enhanced OSCC growth in vivo. Finally, increased PNI focus number was found dose-dependently associated with increased cervical lymph node metastasis and decreased 5-year disease-specific survival rates. Conclusions These results clearly indicated the presence of nerve-tumour interaction that involved paracrine influences leading to aggressiveness of OSCC. Further investigations are required to explore key cell types and molecules involved in nerve-tumour interactions for future therapeutic targeting of PNI in OSCC.

PD-L1 expression is critical in helping tumor cells evade the immune system. However, the level of PD-L1 expression in non-oropharyngeal head and neck squamous cell carcinoma (non-OPHNSCC) and its association with patient prognosis remains unclear. A retrospective clinicopathological analysis was performed on 106 patients with non-OPHNSCC diagnosed between 2007 and 2014. In the current study, tissue arrays from paraffin-embedded non-OPHNSCC samples obtained from patients were constructed, and PD-L1 and p16INK4A expression were determined using immunohistochemistry. Systemic inflammatory factors, including C-reactive protein, serum white blood cell, neutrophil, monocyte and lymphocyte counts were also analyzed. The current study demonstrated that PD-L1 was overexpressed in 32.1% (34/106) and p16INK4A in 20.8% (22/106) of patients. The expression of PD-L1 was associated with p16INK4A expression (P

The aim of this study is to introduce pterygomandibular suspension suture as a simple modification of uvulopalatopharyngoplasty for severe obstructive sleep apnea in dealing with lateral pharyngeal wall and retropalatal space collapse. This retrospective study was conducted at Taipei Veterans General Hospital, Taiwan. Ten adult patients underwent modified uvulopalatopharyngoplasty with pterygomandibular suspension suture according to following inclusion criteria: severe obstructive sleep apnea (apnea–hypopnea index [AHI] > 30 events/h), type I Fujita with lateral pharyngeal wall collapse, and failure for continuous positive airway pressure (CPAP) therapy. The philosophy of this modification technique is to create a firm anterolateral suspension of the lateral pharyngeal wall and soft palate by sutures. The mean operative time of modified uvulopalatopharyngoplasty with pterygomandibular suspension suture was 60 min. The mean AHI decreased significantly from 77.2 ± 25.0 preoperatively to 28.7 ± 18.8 postoperatively (P = 0.005) and the lowest oxygen saturation increased from 69.9 ± 11.4 to 81.1 ± 7.19% (P = 0.005). No major perioperative complication such as massive bleeding or respiratory distress was noted. No patient experienced a swallowing disturbance, taste change, or voice change 6 months postoperatively. The mean period for resuming a normal diet was 15 days. Modified uvulopalatopharyngoplasty with pterygomandibular suspension suture is a simplified and effective surgical approach with satisfactory functional recovery for selective patients with severe obstructive sleep apnea.

// Yi-Fen Wang 1,2 , Chun-Ju Chang 3 , Jen-Hwey Chiu 4 , Chin-Ping Lin 5 , Wing-Yin Li 2,6 , Shyue-Yih Chang 1 , Pen-Yuan Chu 1,2 , Shyh-Kuan Tai 1,2 , Yu-Jen Chen 4,5,7 1 Department of Otorhinolaryngology and Head and Neck Surgery, Taipei Veterans General Hospital, Taipei, Taiwan 2 Department of Medicine, National Yang Ming University, Taipei, Taiwan 3 Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan 4 Institute of Traditional Medicine, National Yang Ming University, Taipei, Taiwan 5 Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan 6 Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan 7 Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan Correspondence: Chun-Ju Chang, email: // Yu-Jen Chen,, email: // Keywords : Head and neck squamous cell carcinoma (HNSCC); NM23-H1; Metastasis; Cisplatin; Prognosis Received : February 20, 2014 Accepted : April 16, 2014 Published : April 18, 2014 Abstract We recently reported that low NM23-H1 expression of head and neck squamous cell carcinoma (HNSCC) correlated with poor patients’ prognosis. Growing evidence has indicated that high tumor NM23-H1 expression contributes to a good response to chemotherapy. Therefore, we investigated the role of NM23-H1 in susceptibility of HNSCC cells to cisplatin and its clinical significance, as well as the in vitro study for validation was performed. Using immunohistochemistry, we analyzed NM23-H1 expression in surgical specimens from 46 HNSCC patients with cervical metastases receiving surgery and adjuvant chemoradiotherapy. Low tumor NM23-H1 expression correlated with locoregional recurrence of HNSCC following postoperative cisplatin-based therapy (p = 0.056) and poor patient prognosis (p = 0.001). To validate the clinical observation and the effect of NM23-H1 on cisplatin cytotoxicity, we established several stable clones derived from a human HNSCC cell line (SAS) by knockdown and overexpression. Knockdown of NM23-H1 attenuated the chemosensitivity of SAS cells to cisplatin, which was associated with reduced cisplatin-induced S-phase accumulation and downregulation of cyclin E1 and A. Overexpression of NM23-H1 reversed these results, indicating the essential role of NM23-H1 in treatment response to cisplatin. NM23-H1 may participate in HNSCC cell responses to cisplatin and be considered a potential therapeutic target.

Observation or elective neck dissection (END) for cN0 neck remains controversial for the treatment of T1-2 oral squamous cell carcinoma (OSCC). Perineural invasion (PNI) has been recognized as a poor prognostic factor for OSCC. However, its significance in T1 OSCC remains unclear. A detailed histologic reevaluation of PNI was carried out in 307 patients with T1-2 OSCC who received surgical treatment between June 2001 and January 2009. We found that the presence of PNI correlated with cervical lymph node metastasis in both T1 and T2 OSCC, with a lower PNI-positive rate in T1 (17.1% vs. 36.6%; P

Neck management for cN0 neck remains controversial for T1-2 oral tongue and buccal squamous cell carcinoma (SCC). Increased tumor thickness and perineural invasion (PNI) are two pathologic features that correlated with cervical lymph node (LN) metastasis and poor survival. However, the relationships between these two features remain unclear.Detailed histologic reevaluation under hematoxylin and eosin staining was performed in tumors of 212 consecutive patients with T1-2, cN0 oral tongue and buccal SCC. The interrelationships between the impacts of tumor thickness and PNI on cervical LN metastasis and disease-specific survival (DSS) were analyzed.Increased tumor thickness (6 mm) correlated with higher LN metastasis and poor 5-year DSS rates in univariate analysis. However, only PNI independently predicted both in multivariate analysis (P = 0.004 and P = 0.039, respectively). When stratified by PNI status, increased tumor thickness did not correlate with higher LN metastasis rate in either PNI-negative or PNI-positive groups (P = 0.337 and P = 0.730). Compared to patients with thin tumors (≤6 mm), patient with thick tumors revealed significantly higher LN metastasis rate (41.9 vs. 16.4 %, P = 0.001) and lower 5-year DSS rate (77.5 vs. 93.7 %, P = 0.006) only at the presence of PNI.PNI can be a major determinant for higher LN metastasis and poor 5-year DSS rates associated with increased tumor thickness in T1-2 oral tongue and buccal SCC. Careful evaluation of PNI should be mandatory in routine pathologic examination, aside from the measurement of tumor thickness.

Background Identification of predictors for permanent facial nerve dysfunction and timing of recovery are important for the management of patients who experience immediate facial nerve dysfunction after parotidectomy. Methods In this 6-year retrospective cohort study, 54 such patients were analyzed to determine the associated prognostic factors and timing of recovery. Results All 54 patients with immediate postparotidectomy facial nerve dysfunction experienced weakness of the marginal mandibular branch; 7% had coexisting zygomatic branch dysfunction. Forty-five patients (83%) achieved complete recovery. The cumulative rates of recovery at 1 month, 3 months, 6 months, and 1 year postparotidectomy were 31%, 70%, 81%, and 83%, respectively. Immediate postparotidectomy facial nerve dysfunction higher than House–Brackmann (H–B) grade III was the only poor prognostic factor (odds ratio, 6.6; 95% confidence interval, 1.2–35.4). Advanced age, malignant tumor, larger tumor size, and postoperative steroids did not exert significant effect on the recovery of facial nerve dysfunction. Conclusion Immediate postparotidectomy facial nerve dysfunction greater than H–B grade III was a significant predictor of permanent dysfunction. Only 2% of patients achieved any improvement beyond 6 months postoperatively. © 2013 Wiley Periodicals, Inc. Head Neck 36: 247–251, 2014

Background The optimal treatment for tonsillar squamous cell carcinoma (SCC) remains controversial. The purpose of this study was to evaluate long-term treatment outcomes of patients with tonsillar SCC, in order to aid in appropriate treatment selection. Methods We conducted a retrospective chart review of 105 patients with curatively treated tonsillar SCC between January 1996 and December 2005. Forty-three patients (41.0%) underwent primary surgery with or without adjuvant therapy (primary surgery group), and 62 patients (59.0%) were treated with radiotherapy/chemoradiotherapy (RT/CRT, organ preservation group). Twenty patients (19%) received tumor tonsillectomy before definitive RT/CRT and were grouped into the organ preservation group. Results No significant differences were observed between the primary surgery and organ preservation groups in terms of local control ( p = 0.212), regional control ( p = 0.684), distant metastasis ( p = 0.627), 5-year disease-specific survival (DSS, p = 0.774), and overall survival rates (OS, p = 0.667). The rates of major complication ( p = 0.216), long-term dependency on feeding tubes ( p = 0.876), and tracheostomy ( p = 0.401) were also similar. Advanced T classification (T3–4) was the only factor associated with significantly worse DSS ( p = 0.007) and OS ( p = 0.012). However, there was also no difference in final treatment outcomes in T3–4 patients regardless of whether they were treated with primary surgery or RT/CRT. In the organ preservation group, tumor tonsillectomy before RT/CRT did not improve local control ( p = 0.520) or other treatment outcomes, including 5-year DSS ( p = 0.707) and OS ( p = 0.745). Conclusion Both primary surgery and RT/CRT organ preservation are effective treatments for tonsillar SCC. Single modality treatment, either surgery or RT/CRT, can typically be provided for stage I–II diseases. Although RT/CRT organ preservation is used more frequently for stage III–IV tonsillar SCC in recent years, primary surgery combined with adjuvant therapy still achieves equivalent outcomes. Multidisciplinary pretreatment counseling and the facilities and personnel available are therefore important for decision-making. In addition, if RT/CRT organ preservation is selected as the primary treatment, tumor tonsillectomy is not indicated.

Chromosomal instability (CIN) is widely considered a hallmark of cancer, but its precise roles in cancer stem cells (CSC) and malignant progression remain uncertain. BMI1 is a member of the Polycomb group of chromatin-modifier proteins that is essential for stem cell self-renewal. In human cancers, BMI1 overexpression drives stem-like properties associated with induction of epithelial–mesenchymal transition (EMT) that promotes invasion, metastasis, and poor prognosis. Here, we report that BMI1 mediates its diverse effects through upregulation of the mitotic kinase Aurora A, which is encoded by the AURKA gene. Two mechanisms were found to be responsible for BMI1-induced AURKA expression. First, BMI1 activated the Akt pathway, thereby upregulating AURKA expression through activation of the β-catenin/TCF4 transcription factor complex. Second, BMI1 repressed miRNA let-7i through a Polycomb complex-dependent mechanism, thereby relieving AURKA expression from let-7i suppression. AURKA upregulation by BMI1 exerts several effects, including centrosomal amplification and aneuploidy, antiapoptosis, and cell-cycle progression through p53 degradation and EMT through stabilization of Snail. Inhibiting Aurora A kinase activity attenuated BMI1-induced tumor growth in vivo. In clinical specimens of head and neck cancer, we found that coamplification of BMI1 and AURKA correlated with poorer prognosis. Together, our results link CSCs, EMT, and CIN through the BMI1–AURKA axis and suggest therapeutic use from inhibiting Aurora A in head and neck cancers, which overexpress BMI1. Cancer Res; 73(2); 953–66. ©2012 AACR.

Objectives Perineural invasion (PNI) is an established poor prognostic pathological feature for oral squamous cell carcinoma (OSCC). The purpose of this study was to analyze the role of pretreatment parameters in predicting PNI for OSCC. Materials and methods We prospectively enrolled into our study 102 newly diagnosed OSCC patients, who were surgically treated from 2011 to 2012. Before treatment, patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire H&N35 and the visual analogue scale (VAS) for cancer pain. Pathological examination was performed to ascertain PNI status in all patients. Patients were divided into two groups, those with PNI and without PNI. Pretreatment parameters were compared between the two groups. Results In univariate analysis, clinical T classification ( P P = 0.001), problem with social eating ( P P = 0.002), VAS scores of primary pain ( P P = 0.004) were found to be associated with PNI. Multivariate logistic regression analysis further revealed VAS score of primary pain ( P = 0.001, OR 2.014) and T3-4 classification ( P = 0.014, OR 6.422) were independent predictors of PNI. A regression equation incorporating pretreatment pain was developed to predict the probability of having PNI. Conclusion PNI can be predicted by higher pretreatment VAS score of primary pain, as well as more advanced clinical T classification. Careful evaluation of pretreatment pain of primary tumor can thus be helpful in improving treatment decision making for OSCC.

Background. Recent studies have indicated hedgehog pathway plays a role in carcinogenesis of certain cancers. We investigated the clinical significance of its signal- ing components, including Sonic hedgehog (Shh), Patched (Ptch), and Gli-1, in oral squamous cell carcinoma (OSCC). Methods. By immunohistochemistry, we determined Shh, Ptch, and Gli-1 expression in surgical specimens from 40 patients with OSCC. The relationship between expression of these molecules and clinicopathologic variables were assessed by chi-square analysis. Statistical difference of sur- vival was compared using log-rank test. Results. Ptch overexpression was associated with lym- phatic metastasis (p ¼ .028). Nuclear Gli-1 overexpression cor- related with primary tumor size (p ¼ .001), lymphatic metastasis (p ¼ .011), and tumor recurrence (p ¼ .008). Over- expression of Ptch (p ¼ .020) or Gli-1 (p ¼ .002) in OSCC indi- cated poor prognosis in the univariate survival analysis. Conclusion. Our results suggest sonic hedgehog (Shh) pathway plays an important role in OSCC progression and should be considered a potential therapeutic target. V C 2012 Wiley Periodicals, Inc. Head Neck 00: 000-000, 2012

To reduce severe acute and late toxicities without compromising organ preservation survival in patients with locoregionally advanced head and neck squamous cell carcinoma, we performed three-drug induction methotrexate-cisplatin-fluorouracil with weekly cisplatin-fluorouracil concurrent chemoradiation.Two induction courses of methotrexate (40 mg/m(2)/day, days 1, 8 and 15), cisplatin and 5-fluorouracil (25 and 750 mg/m(2)/day, days 1-4) were given in new diagnoses of patients with non-nasopharyngeal locoregionally advanced head and neck squamous cell carcinoma. Responders received concurrent chemoradiation with weekly cisplatin (20 mg/m(2)/day) and 5-fluorouracil (400 mg/m(2)/day) on day 1.Among 57 patients (58% with Stage IV and hypopharyngeal cancer), the rates of Grade 3-4 toxicity were 30 and 74% during induction and CCRT, respectively. A total of 49 patients completed induction and began concurrent chemoradiation; 47 (96%) completed all planned treatment. With a median follow-up of 62 months (range 19-83 months) for the current survivors, the 3-year overall and disease-specific survival estimates were 50 and 58%, respectively. The 3-year organ preservation survival was 74% in patients who achieved complete remission after concurrent chemoradiation, and 96% of current survivors are tracheotomy and feeding tube-free. No patient without local/regional failure suffered from distant metastasis.Methotrexate-cisplatin-fluorouracil induction chemotherapy followed by weekly cisplatin-fluorouracil concurrent chemoradiation is an acute and late toxicity-acceptable protocol without attenuating organ preservation survival in patients with locoregionally advanced head and neck squamous cell carcinoma. In this patient cohort with advanced head and neck squamous cell carcinoma, overall and organ preservation survivals were encouraging, and provided promising long-term benefits of this approach.

The efficacy and safety of gemcitabine in combination with cisplatin (GC) as the first-line treatment in patients with recurrent/metastatic (R/M) squamous cell carcinoma of head and neck (SCCHN) was examined.Patients with R/M SCCHN without prior treatment for their R/M disease were eligible and treated with gemcitabine 1,250 mg/m(2) on day 1, day 8 and cisplatin 80 mg/m(2) on day 8 every 21 days.Forty patients were enrolled from March 2004 to January 2006, and 30 were evaluable for treatment effectiveness and outcome. The median age of evaluable patients was 50 years and all patients were male. Partial response was observed in 9 (30%) and stable disease in 7 (23.3%) patients. The overall response rate and disease control rate was 30 and 53.3%, respectively. The major toxic effects were ≥grade 3 leukopenia and anemia (65 and 27.5%, respectively). With a follow-up of 72 months, the median time to progression (TTP) was 128 days (95% CI, 78-242) and median overall survival (OS) was 401 days (95% CI, 216 approximately not reached).This GC regimen demonstrates a good activity and a promising survival period in patients with R/M SCCHN.

Background. We assessed the role of 18F-fluoro-deoxy-glucose positron emission tomography (PET) in detecting head and neck squamous cell carcinoma (HNSCC) after definitive chemoradiotherapy (CRT). Methods. A prospective study presented 80 PET before and after CRT for 44 patients, including 44 first-time post-CRT scans performed between 12 and 17 weeks after radiotherapy completion, as well as 10 repeated scans in the subsequent follow-up. PET interpretations were compared with clinicopathologic outcomes. Results. PET demonstrated better performance than CT in post-CRT surveillance. Considering all 54 post-CRT PET scans, sensitivity for detecting primary tumors was 100%, specificity 93%, positive predictive value (PPV) 80%, and negative predictive value (NPV) 100%. For cervical diseases, sensitivity was 100%, specificity 98%, PPV 92%, and NPV 100%. For distant metastases, sensitivity was 100%, specificity 98%, PPV 86%, and NPV 100%. Conclusions. Negative PET readings were reliable for predicting free of HNSCC and helpful for selected patients in post-CRT surveillance. © 2009 Wiley Periodicals, Inc. Head Neck, 2009

Objective: Laryngeal preservation is a challenge for the treatment of advanced hypopharyngeal cancer. The objective of this study is to evaluate the results of chemoradiotherapy laryngeal preservation for advanced hypopharyngeal cancer at a single institute and the impact of treatment factors on prognosis. Methods: The study population consisted of 42 consecutive patients with resectable stage III–IV hypopharyngeal cancer. Patients with T4b tumor, synchronous primary cancer or those treated palliatively were excluded. Induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) was performed in 32 (76.2%) patients, whereas primary CCRT was done in the other 10 (23.8%). Patients were grouped according to the dose intensity of chemotherapy and total dose of radiotherapy (RT). Results: Grade 3 –4 toxicities occurred mostly during CCRT. Thirty-five (83.3%) patients received an optimum dose of cisplatin (CT-optimum), 27 (64.3%) received an optimum dose of RT-optimum and 26 (61.9%) received optimum doses of both (CRT-optimum). CT- and RT-optimum both correlated significantly with better disease-free survival (DFS) (P , 0.001 and ¼ 0.003), overall survival (OS) (P , 0.001 and ¼ 0.004) and laryngeal preservation survival (LPS) (P ¼ 0.01 and 0.04). The 3-year DFS, OS and LPS for CRT-optimum patients were 48.1, 50.0 and 45.6%, respectively. Conclusions: Achievement of optimum treatment dose remains challenging in chemoradiotherapy laryngeal preservation for advanced hypopharyngeal cancer. Intensive patient care and monitoring by experienced multi-disciplinary teamwork are mandatory. The criteria for selecting patients who will respond to and complete the treatment remain key issues for future investigation.

BackgroundTo determine the efficacy and safety profile of the combination of cisplatin and 5-fluorouracil modulatedboth by methotrexate and leucovorin in metastatic/recurrent squamous cell carcinoma of the head and neck.MethodsTwenty-eight patients were treated with cisplatin 40 mg/m2/day continuous infusion for 24 hours on day 1;high-dose 5-fluorouracil 2,000 mg/m2/day and leucovorin 100 mg/m2/day continuous infusion for 48 hours on days 1and 2; methotrexate 40 mg/m2/day as a bolus infusion 4 hours before 5-fluorouracil and leucovorin on day 1. The treat-ment was repeated every 2 weeks in a cycle.ResultsThe overall response rate was 25%, and 14% of the patients achieved stable disease status. Subgroup analy-sis demonstrated significantly improved overall survival in the disease-control group (12.0 months vs. 5.3 months,p < 0.001). Only 3 (10.7%) patients developed grade 3–4 neutropenia, and none developed grade 3–4 non-hematologictoxicity.ConclusionThis multiagent-containing regimen has an excellent safety profile and improved survival in disease-controlgroup of patients with metastatic/recurrent squamous cell carcinoma of the head and neck.

We recently reported that low Nm23-H1 expression of primary oral squamous cell carcinoma (OSCC) was correlated with the occurrence of lymphatic metastasis. However, little is known about whether Nm23-H1 level of metastatic tumors in the cervical lymph nodes is reduced in comparison with primary oral cancers and its significance for patients' prognosis. By immunohistochemistry, we analyzed the Nm23-H1 expression in 52 pairs of OSCC specimens from primary oral cancers and their metastatic lymph nodes. Western blot analysis further confirmed the immunohistochemical interpretation. To verify the effects of Nm23-H1 on cell migration and invasion, we established several stable clones derived from a human OSCC cell line (SAS) by knockdown and overexpression. Wound-healing closure, transwell migration and invasion assays were performed to determine cell motility, migratory and invasive activities. Western blot analysis was carried out to evaluate cyclin A expression of OSCC cells with the altered Nm23-H1 levels following knockdown and overexpression. By immunohistochemistry, Nm23-H1 expression of metastatic lymph nodes was significantly lower than that of their primary oral cancers, supporting a role of Nm23-H1 in metastasis suppression. Negative Nm23-H1 interpretation of OSCC specimens, in either primary oral cancers or metastatic lymph nodes, indicated a poor survival outcome of patients. On the basis of in vitro studies of Nm23-H1 knockdown and overexpression, we demonstrated an inverse correlation between Nm23-H1 expression and the invasiveness of OSCC cells. Moreover, we observed the concomitant reduction in Nm23-H1 and cyclin A levels of metastatic tumors in both results of in vitro OSCC cells and ex vivo tumor specimens.

Background. Triweekly cisplatin-based postoperative concurrent chemoradiotherapy (CCRT) has high intolerance and toxicities in locally advanced head and neck cancer (LAHNC). We evaluated the effect of a modified weekly cisplatin-based chemotherapy in postoperative CCRT.Methods. A total of 117 patients with LAHNC were enrolled between December 2007 and December 2012. Survival, compliance/adverse events, and independent prognostic factors were analyzed.Results. Median follow-up time was 30.0 (3.1–73.0) months. Most patients completed the entire course of postoperative CCRT (radiotherapy ≥ 60 Gy, 94.9%; ≥6 times weekly chemotherapy, 75.2%). Only 17.1% patients required hospital admission. The most common adverse effect was grade 3/4 mucositis (28.2%). No patient died due to protocol-related adverse effects. Multivariate analysis revealed the following independent prognostic factors: oropharyngeal cancer, extracapsular spread, and total radiation dose. Two-year progression-free survival and overall survival rates were 70.9% and 79.5%, respectively.Conclusion. Modified weekly cisplatin-based chemotherapy is an acceptable regimen in postoperative CCRT for LAHNC.

Background Recent studies showed that interleukin-6 (IL-6) played a role in tumor development. However, available information about the prognostic significance of IL-6 and IL-6 receptors (IL-6R) for oral squamous cell carcinoma (OSCC) is limited. Methods Eighty-six patients with OSCC were enrolled. Immunohistochemical staining was used to determine IL-6R expression and in-situ hybridization for IL-6 mRNA transcripts in surgical specimens. Clinicopathologic correlation was evaluated by chi-square test and survival by log rank test. Results Expression rates of IL-6R and IL-6 mRNA transcripts in tumor specimens were 73.3% and 54.7%, much higher than those in nontumor mucosa (p < .001). IL-6R overexpression was associated with larger tumors and more advanced histologic grade (p < .05). The presence of IL-6 mRNA transcripts was inversely correlated with distant metastasis, lymph node involvement, and second primary SCC (p < .05) and predicted better survival (p = .007). Conclusions IL-6-IL-6R coexpression was rather high in OSCC, and IL-6 mRNA transcript expression might influence patient survival. The biologic role of IL-6-IL-6R coexpression in OSCC needs additional investigation. © 2002 Wiley Periodicals, Inc. Head Neck 24: 850–858, 2002

Summary Objectives Management of cN0 neck, elective neck dissection (END) or observation, remains controversial for T1–2 oral squamous cell carcinoma (OSCC). To allow for the safe observation of cN0 neck, it is mandatory to define predictors with high negative predictive value (NPV) for cervical lymph node (LN) status. Materials and Methods Pathologic re-evaluation was performed in tumors of 253 consecutive patients with T1–2, cN0 OSCC. The predictive roles of pathologic parameters for cervical LN status in guiding neck management were investigated. Results Cervical LN metastasis (LN+) occurred at a similar rate between observation and END groups (20.8% vs. 22.2%, p = 0.807), indicating poor discriminatory value for cervical LN status by clinical judgment. Compared with T classification, tumor thickness and differentiation, PNI/LVI (perineural invasion/lymphovascular invasion) demonstrated the highest NPV (85.5%). Hypothetically using PNI/LVI status to guide neck management, a dramatic reduction in overtreatment rate could be achieved (54.2% to 20.2%), with a minimal increase in undertreatment rate (6.3% to 9.9%). In patients without PNI or LVI (PNI/LVI−), the ultimate neck control rate (96.9% vs. 96.3%, p = 1.000) and 5-year disease-specific survival rate (91.1% vs. 92.8%, p = 0.863) were equivalent between observation and END. However, a significantly higher incidence of neck recurrence was found with observation (16.9% vs. 6.5%, p = 0.031), with 93.8% occurring within one year and 73.3% being successfully salvaged. Conclusion Observation under close follow-up for the first year is appropriate in T1–2, cN0 OSCC without PNI or LVI, for the achievement of equivalent ultimate neck control and 5-year disease-specific survival rates compared with END.

Although direct microlaryngoscopic surgery is universally accepted as the standard procedure for endolaryngeal surgery, general anesthesia and direct laryngoscopy are necessary during the procedure. Suspended laryngeal position also impedes intraoperative functional monitoring. Transoral laryngeal surgery under indirect laryngeal mirror or telescope has the advantage of sparing general anesthesia and direct laryngoscopy, but lower precision, difficult manipulation, and a high patient cooperation requirement make the procedure of limited application. Trying to overcome the above shortcomings, transoral laryngeal surgery under flexible laryngovideostroboscopy (FLVS) is undertaken at our institute. The surgery is performed at an outpatient office under topical anesthesia, with the help of high-resolution fiberoptic stroboscopy, high-quality CCD videocamera, and monitor. From October, 1993 to March, 1996, 157 patients with selected laryngeal problems were operated upon using this technique, and 150 patients smoothly completed the procedure with satisfactory results. The technique is highly effective, especially for limited-manipulation, lower precision procedures and for patients who are not candidates for general anesthesia. With proper patient selection, this is a cost-effective surgery of low invasiveness and high applicability.

The epithelial–mesenchymal transition (EMT) is a key mechanism in both embryonic development and cancer metastasis. The EMT introduces stem-like properties to cancer cells. However, during somatic cell reprogramming, mesenchymal–epithelial transition (MET), the reverse process of EMT, is a crucial step toward pluripotency. Connective tissue growth factor (CTGF) is a multifunctional secreted protein that acts as either an oncoprotein or a tumor suppressor among different cancers. Here, we show that in head and neck squamous cell carcinoma (HNSCC), CTGF promotes the MET and reduces invasiveness. Moreover, we found that CTGF enhances the stem-like properties of HNSCC cells and increases the expression of multiple pluripotency genes. Mechanistic studies showed that CTGF induces c-Jun expression through αvβ3 integrin and that c-Jun directly activates the transcription of the pluripotency genes NANOG, SOX2, and POU5F1. Knockdown of CTGF in TW2.6 cells was shown to reduce tumor formation and attenuate E-cadherin expression in xenotransplanted tumors. In HNSCC patient samples, CTGF expression was positively correlated with the levels of CDH1, NANOG, SOX2, and POU5F1. Coexpression of CTGF and the pluripotency genes was found to be associated with a worse prognosis. These findings are valuable in elucidating the interplay between epithelial plasticity and stem-like properties during cancer progression and provide useful information for developing a novel classification system and therapeutic strategies for HNSCC. Cancer Res; 73(13); 4147–57. ©2013 AACR.

Objective: Carotid blowout syndrome is a severe complication of head and neck cancer. High mortality and major neurologic morbidity are associated with carotid blowout syndrome with massive bleeding. Prediction of outcomes for carotid blowout syndrome patients is important for clinicians, especially for patients with the risk of massive bleeding. Methods: Between 1 January 2001 and 31 December 2011, 103 patients with carotid blowout syndrome were enrolled in this study. The patients were divided into groups with and without massive bleeding. Prognostic factors were analysed with proportional hazard (Cox) regressions for carotid blowout syndrome-related prognoses. Survival analyses were based on the time from diagnosis of carotid blowout syndrome to massive bleeding and death. Results: Patients with massive bleeding were more likely to have hypoalbuminemia (albumin ,3.5 g/dl; P ¼ 0.023). Univariate analysis of carotid blowout syndrome-related massive bleeding showed that treatment for carotid blowout syndrome (best supportive care, P ¼ 0.000; embolization, P ¼ 0.000), monocytosis (monocytes .1000 cells/ml, P ¼ 0.041) and hypoalbuminemia (P ¼ 0.010) were important to prognosis. Concurrent chemoradiotherapy (P ¼ 0.007), elevated lactate dehydrogenase (.250 U/l; P ¼ 0.050), local recurrence (P ¼ 0.022) and hypoalbuminemia (P ¼ 0.038) were related to poor prognosis in carotid blowout syndrome-related death. In multivariate analysis, best supportive care and hypoalbuminemia were independent factors for both carotid blowout syndrome-related massive bleeding (P ¼ 0.000) and carotid blowout syndrome-related death (P ¼ 0.013), respectively. Conclusion: Best supportive care and serum albumin are important prognostic factors in carotid blowout syndrome. It helps clinicians to evaluate and provide better supportive care for these patients.

Although perineural invasion (PNI) has been a poor prognostic factor for head and neck cancers, few studies have focused on oral squamous cell carcinoma (OSCC). The independent significance of PNI in early T1-2 OSCC and the benefit of treatment modification based on PNI status have not been assessed. This study investigated the role of PNI in T1-2 OSCC patients, with focus on the controversial issues of neck management and postoperative adjuvant therapy. PNI status was re-reviewed under hematoxylin and eosin staining in tumors of 307 consecutive T1-2 OSCC patients. Oncologic and survival outcomes were analyzed by univariate and multivariate analyses. PNI was identified in 84 (27.4%) patients, correlating with several established poor prognostic factors. In multivariate analysis, PNI remained an independent predictor for neck metastasis, neck recurrence, and a worse 5-year disease-specific survival. Elective neck dissection contributed to a significantly better 5-year disease-specific survival only in cN0 patients with PNI-positive tumors (P = 0.0071) but not in those with PNI-negative tumors (P = 0.3566). In low-risk patients who were treated by surgery alone, including neck dissection, the 5-year disease-specific survival rates were almost the same in those with PNI-positive tumors and those with PNI-negative tumors (92.0 vs. 92.9%; P = 0.9104). Elective neck dissection is indicated for cN0 patients with PNI-positive tumors for the efficacy of improving disease-specific survival as well as neck control. However, low-risk PNI-positive patients who undergo neck dissection do not need postoperative adjuvant therapy, because the residual risk from PNI is minimal.

Background Risks of perineural invasion (PNI) in T1-2 oral tongue squamous cell carcinoma (SCC) have not been specifically elucidated. Methods Pathological features, including PNI, were re-reviewed under regular hematoxylin-eosin staining in 190 patients with T1-2 oral tongue SCC. Results Tumor thickness >5 mm, PNI(+), and lymphovascular invasion (+) independently predicted lymph node involvement. PNI(+) and neck observation also independently predicted neck recurrence, but only PNI(+) was associated with a poor disease-specific survival (DSS; p = .003). In patients who were clinically node negative (cN0), elective neck dissection contributed to a better DSS in patients with PNI(+) tumors (p = .046), but not in patients with PNI (-) tumors (p = .809). Additionally, increased tumor thickness predicted the presence of PNI. Conclusion PNI is a crucial pathological feature for T1-2 oral tongue SCC. Elective neck dissection should be performed in patients who were cN0 with PNI. Careful evaluation for PNI should be advocated in regular pathological diagnosis. © 2011 Wiley Periodicals, Inc. Head Neck, 2012

Pleomorphic adenomas, or benign mixed tumors, make up 65% of all salivary gland tumors. They also can be found as solid tumors in other parts of the head and neck region, such as the auditory canal, the eyelids, and the orbital area. In this study, we investigated extra-major salivary gland pleomorphic adenomas of the head and neck region retrospectively at a tertiary care center. Between March 1998 and June 2009, 37 patients underwent primary surgery for extra-major salivary gland pleomorphic adenoma of the head and neck. The duration of symptoms, radiographic findings, operative procedures, and pathologic findings were documented. Of the 37 patients enrolled, 22 were male and 15 were female, with a median age of 57 years. Tumors were found in the soft palate, hard palate, nasopharynx, orbital area, trachea, buccal mucosa, cheek, nasal septum, upper lip, lower eyelid, and external auditory canal. Cellular variant of the pleomorphic adenoma was found in four patients, while the remaining patients presented with the classic variant. No myxoid subgroup was noted in our study. Carcinoma ex pleomorphic adenoma was observed only in one patient for whom radical surgery was performed. Twenty-eight patients (76%) had long-term follow-ups, with the average follow-up period being 4.5 years. Local recurrence was observed in three patients, and they underwent revision surgery during the follow-up period. Our results indicate that extra-major salivary gland pleomorphic adenomas are most commonly found in the soft palate. Wide excision was the treatment of choice, although its efficacy might be compromised with cosmetics and functional structures of the head and neck. Therefore, long-term follow-up of patients is necessary.

Background We evaluated the effectiveness of narrow band imaging (NBI) in patients with oral squamous cell carcinoma (OSCC) after treatment. Methods In all, 101 consecutive OSCC patients underwent NBI examination for posttreatment follow-up. Four patients had local recurrence. Twenty-six second primary malignancies were found in 18 patients; 6 patients (33%) had more than 1 lesion. Seventeen lesions (65%) were carcinoma in situ or severe dysplasia. Most of them occurred in the oral cavity (77%). Results A higher incidence (18% vs 9%, p = .037) and less-advanced stage (4% vs 37%, p = .0005) of second primary malignancies were found among the NBI group compared with a previous cohort without NBI examination, and fewer patients needed postoperative adjuvant therapy (12% vs 50%, p = .0005). Conclusions NBI is an effective method to identify early lesions in the head and neck area, especially the oral cavity, among patients with OSCC after treatment. © 2011 Wiley Periodicals, Inc. Head Neck, 2012

Purpose The aim of the present study was to compare the incidence, patterns, and survival of second primary malignancy (SPM) in patients with squamous cell carcinoma of the larynx (LSCC) and hypopharynx (HPSCC). Methods We retrospectively review the medical record of 581 previously untreated patients with LSCC (392 cases) and HPSCC (189 cases) who received primary surgery with or without postoperative radiotherapy from 1990 to 2000. Data including age, sex, risk factors, subsites and TNM stage of primary tumor, treatment, site and incidence of SPM, and prognosis were collected from medical charts. Results Groups with HPSCC had a higher incidence (4.2% vs 2.9% annual rate) and shorter median time (30 vs 59 months) developing SPM rather than LSCC. Fifty-five percent of the SPM occurred in the respiratory axis in LSCC, and 66% developed in the digestive axis in HPSCC. The factors influencing the appearance of SPM included early T stage, tobacco use, and less tumor recurrence. Long-term survival was poorer in those with than without SPM (38% vs 49% at 10 years). Conclusions There is a tendency for SPM to occur in the respiratory axis (lung and larynx) in LSCC and in the digestive axis (oral cavity, pharynx, and esophagus) in HPSCC. This information is important for posttreatment follow-up.

Objectives: To evaluate the role of chest computed tomography (CT) in patients with head and neck squamous cell carcinoma (HNSCC) and to determine the optimal timing and predictive factors for positive findings. Design: Retrospective analysis. Setting: Tertiary referral center. Patients:TwohundredseventyscreeningchestCTscans performed in 192 patients with HNSCC during a 42month period were reviewed. Main Outcome Measures: The scans were categorized as new cases, follow-up cases, or recurrent cases. The results were classified as abnormal or normal. Scans of patients having a radiologic diagnosis of a malignant neoplasmofthelungoranindeterminatelesionwereconsidered abnormal. Factors correlating with an abnormal chest CT scan or development of malignant neoplasm of the lung were analyzed, including the timing of imaging and the patients’ clinicopathologic data. Results: Seventy-nine scans (29.3%) were considered abnormal. The rate of an abnormal scan was significantly higher in the follow-up case group (44.2%) than in the new case group (14.2%) (P.001). Ten of 15 indeterminate scans (66.7%) with small (1 cm) solitary pulmonary nodules showed disease progression on subsequent follow-up scans, changing the patients’ diagnoses to a malignant neoplasm of the lung. The predictive factors for development of a malignant neoplasm of the lung were initial N2 or N3 disease, stage IV disease, recurrent disease, and distant metastasis to another site. Conclusions: Chest CT is recommended for high-risk patients, especially during the follow-up period. Intensified evaluation and management are mandatory for indeterminate small solitary pulmonary nodules because of the high rate of malignant neoplasms.

To test the efficacy and safety of pharmacokinetic modulating chemotherapy combined with cisplatin (PMC-cisplatin) as induction chemotherapy (ICT) before definitive treatment in patients with respectable locally advanced head and neck squamous cell carcinoma (HNSCC).Patients with stage III-IV resectable locally advanced HNSCC were enrolled. All eligible patients received PMC-cisplatin regimen as ICT containing intravenous leucovorin 250 mg/m(2) and 5-FU 600 mg/m(2) on day 1, oral tegafur-uracil (UFUR) 250 mg/m(2)/day on days 1-5, repeated every week for six courses. Cisplatin 100 mg/m(2 )was given during the first and fourth courses of PMC. For ICT responders, concurrent chemoradiotherapy (CRT) with cisplatin/tegafur-uracil/70 Gy radiotherapy was performed. Salvage surgery plus postoperative CRT was given to ICT non-responders.The overall response rate of PMC-cisplatin as ICT was 76%, including a complete remission rate of 23%. The overall organ preservation rate of the multimodality treatment was 75%, with 97% in ICT responders. At a median follow-up of 25 months, 47% of the patients were still alive and disease-free. The superiority of disease-free survival was demonstrated in ICT responders. The 3-year overall survival rate was 67%. The toxicity of treatment was acceptable.Application of PMC-cisplatin as the induction chemotherapy before definitive treatment provides a promising result in treatment response and survival of advanced HNSCC. This regimen is effective and safe, and further studies considering the combination of PMC with other chemotherapeutics such as taxanes to improve the clinical outcome of advanced HNSCC is warranted.

e17016 Background: The managements for unresectable oral cancer are difficult because of the chemo- and radioresistance. Such resistance may be due to complex environmental carcinogens such as alco...

Trente-sept patients porteurs de cancer des deux tiers anterieurs de la langue sans signe d'atteinte des ganglions cervicaux ou de metastases a distance ont ete traites par microchirurgie au laser CO 2 . Durant l'intervention, un appareil de succion-coagulation monopolaire est aussi utilise pour obtenir un champ chirurgical propre. Sous microscopie, nous palpons de facon repetitive les tissus mous de facon a bien identifier les marges de la tumeur, en particulier la marge profonde, de facon a maintenir une distance securitaire adequate dans les trois dimensions. Nous faisons la resection de la tumeur en bloc plutot que de la vaporiser ou de reduire simplement son volume. Des 28 patients dans le groupe T1 et T2, 26 patients n'ont pas recu de radiotherapie post-operatoire. Le taux de controle local, calcule selon la methode Kaplan et Meier, chez ces 37 patients est de 93.6% a 5 ans. Aucune recidive locale n'a ete notee dans les cas de T1 ou T2. Neuf patients ont par contre presente des recidives cervicales et le taux de controle a ce niveau est de 74.6% a 5 ans. Huit de ces 9 patients ont ete rattrapes par chirurgie avec radiotherapie adjuvante et 6 ont finalement ete gueris. Le taux de survie sans maladie a 5 ans pour notre serie est de 88%. Notre technique chirurgicale utilisant la microchirurgie a l'aide du laser au CO 2 est efficace et est une methode avantageuse pour l'excision des cancers de la langue orale en particulier pour les stades 1 et 2.

Purpose Management of cN0 neck remains controversial for T1-2 OSCC (oral squamous cell carcinoma). Perineural invasion (PNI) has been a poor prognostic factor for OSCC, but its significance in T1 OSCC remains unclear. This study investigated the role of PNI, focusing on the controversial issues of neck management in T1 OSCC patients. Materials and methods PNI status was re-evaluated under hematoxylin and eosin staining in tumors of 307 consecutive T1-2 OSCC patients who received surgical treatment. Oncologic and survival outcomes were compared between T1 and T2 patients. Impacts of PNI in T1 OSCC were analyzed by univariate and multivariate analyses. Results The presence of PNI correlated with cervical LN metastasis in both T1 and T2 OSCC, and PNI-positive rate was significantly lower in T1 (17.1% versus 36.6%; P P P P P = 0.399 and P = 0.1478). Of the 146 patients with T1 OSCC, PNI remained independently predictive of cervical LN metastasis, neck recurrence and poor DSS. Elective neck dissection significantly reduced neck recurrence in PNI-positive ( P = 0.001) but not in PNI-negative patients ( P = 0.114). Elective neck dissection also improved the 5-year DSS rate more obvious, although not statistically significant, in PNI-positive than in PNI-negative patients (16.2% versus 5.4%). Conclusions PNI independently predicts poor prognosis in patients with T1 OSCC who are potentially curable but tend to be treated conservatively. Elective neck dissection should be performed for T1, PNI-positive patients for its efficacy in improving neck recurrence and survival.

Background: Head and neck cancer patients have a higher risk of developing a second primary malignancy (SPM) than the general population. This study was conducted to identify the characteristics of SPM and its impact on survival in patients with squamous cell carcinoma of the tongue (TSCC) and larynx (LSCC). Methods: A retrospective study was conducted of 538 patients who were treated by surgery primarily for TSCC (n = 146) and LSCC (n = 392) from 1990 to 2000. The incidence, site, and overall survival of SPMs were evaluated. Results: Seventy-seven patients developed SPM during the follow-up period (median, 73 months), including 18 (12%) with TSCC and 59 (15%) with LSCC. Fifty-six percent of SPMs of the TSCC group appeared in the oral cavity. Among the SPMs of LSCC patients, 54% developed in the lung (31%) and larynx (24%). The 5-year overall survival after the diagnosis of SPM in the head and neck was 39%, compared to 29% for SPM in other areas (p = 0.010). Conclusion: SPMs after treatment of TSCC and LSCC are similar in incidence but distinct in pattern. SPMs within the head and neck are associated with a better prognosis than those outside this area. [J Chin Med Assoc 2008; 71(2):86–91]

Background The optimal treatment of base of tongue squamous cell carcinoma (BOTSCC) remains controversial. To optimize treatment planning, this study analyzed the outcomes of patients with BOTSCC treated in Taipei Veterans General Hospital. Methods Retrospective chart reviews were performed for 107 patients with BOTSCC from January 1990 to December 2004, and 85 patients were included, with a mean follow-up interval of 38 months. Patients were divided into surgical and radiotherapy/chemoradiation therapy (RT/CRT) groups. Potentially significant variables for survival were analyzed. Results The 3-year overall survival (OS) and disease-free survival rates were 40% and 37.1%, respectively. No significant differences in the patient and disease characteristics between the surgical ( n = 39) and RT/CRT groups ( n = 46) were found. Advanced overall stage ( p = 0.034), cervical lymph node metastasis ( p = 0.007), and regional recurrence ( p = 0.024) were poor prognostic factors for OS. In early-stage disease (Stages I and II), the 3-year OS was higher in the surgical group (68.6%) than in the RT/CRT group (37.5%), but the significance was only borderline ( p = 0.071). There was no significant difference in the 3-year OS between the patients in the surgical and CT/CRT groups with advanced-stage disease. In the surgical group, lymphovascular permeation ( p = 0.015) and soft-tissue involvement ( p = 0.01), determined by pathologic examination, were poor prognostic factors for OS. Recurrence occurred in 35 patients (41.2%), with no significant difference in local, regional, or distant control between the surgical and RT/CRT groups. Conclusion These findings emphasize the importance of neck disease control in the treatment of BOTSCC. Although currently, RT/CRT is used more frequently, surgery may still have a role in the treatment of early-stage disease. Both surgery with adjuvant therapy and RT/CRT produced equivalent survival rates in the treatment of advanced-stage disease, but the recurrence rate was unsatisfactory. A more effective treatment modality with less early and late toxicity is needed.

BackgroundMassive hemorrhages occur in 6%-10% of patients with advanced cancer. Acute carotid blowout syndrome is the most severe massive hemorrhagic complication in head and neck cancer patients.MethodsThis was a single institute, retrospective, case control study. A total of 45 patients were enrolled in this study. The predisposing factors, management, and prognosis of acute carotid blowout syndrome were evaluated.ResultsAmong the baseline characteristics, the site of the primary tumor (P = .003), origin of bleeding (P = .048), method of intervention (P = .005), and time to intervention (P = .006) were significantly different factors between survivor and nonsurvivor patients. After 24 hours of onset, a Glasgow Coma Scale score (P = .000), the use of inotropic agents (P = .007), and neutrophil-to-lymphocyte ratio (P = .019) were significantly predicting factors for outcome. Multivariate logistic regression analyses revealed bleeding from common carotid artery was an independent factor for long-term survival (odds ratio, 25.951; 95% confidence interval [CI], 1.373-490.441; P < .030). The median overall survival of survivors and nonsurvivors were 12.1 (range, 3.7-118.7; 95% CI, 4.33-54.87) and 11.9 (range, 0.7-53.5; 95% CI, 5.78-25.69) months, respectively (P = .092).ConclusionsEarly and aggressive intervention is important for the successful management of acute carotid blowout syndrome. The Glasgow Coma Scale score, the use of inotropic agents, and neutrophil-to-lymphocyte ratio 24 hours after the onset were predictive factors for patients' outcomes. Bleeding from common carotid artery is an independent prognostic factor in multivariate analysis. Long-term survival can be achieved after successful management.